Survival rates of systemic interventions for psoriasis in the Western Japan Psoriasis Registry: A multicenter retrospective study.

Psoriasis affects approximately 0.3% of the Japanese population. Recently, various effective systemic drugs have become available, and the continuation of a given treatment has become critical because of the chronic nature of psoriasis. Factors affecting drug survival (the time until treatment discontinuation) in psoriasis treatment include efficacy, safety, ease of use, and patient preference. In the present study, the authors retrospectively surveyed a multifacility patient registry to determine the real-world evidence of the survival rate of systemic interventions for psoriasis treatment. Patients with psoriasis who visited 20 facilities in the Western Japan area between January 2019 and May 2020 and gave written consent were registered as study participants, and their medical history of systemic interventions for psoriasis (starting from 2010) was retrospectively collected and analyzed. The drugs investigated were adalimumab, infliximab, ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, cyclosporine, and apremilast. When drugs were discontinued, the reasons were also recorded. A total of 1003 patients with psoriasis including 268 with psoriatic arthritis (PsA) were enrolled. In biologics, more recently released drugs such as interleukin 17 inhibitors showed a numerically higher survival rate in the overall (post-2010) analysis. However, in the subset of patients who began treatment after 2017, the difference in the survival rate among the drugs was smaller. The reasons for discontinuing drugs varied, but a loss of efficacy against dermatological or joint symptoms were relatively frequently seen with some biologics and cyclosporine. The stratification of drug survival rates based on patient characteristics such as bio-naive or experienced, normal weight or obese, and with or without PsA, revealed that bio-experienced, obese, and PsA groups had poorer survival rates for most drugs. No notable safety issues were identified in this study. Overall, the present study revealed that the biologics show differences in their tendency to develop a loss of efficacy, and the factors that negatively impact the survival rate of biologics include the previous use of biologics, obesity, and PsA.

Clinical characteristics of patients with psoriasis with family history: A multicenter observational study.

Previous studies on family history of psoriasis showed that patients with a family history have an earlier onset of the disease, but such studies in Japan are still limited. To elucidate the characteristics of patients with familial psoriasis, we studied the family history of patients with psoriasis using the West Japan Psoriasis Registry, a multi-institutional registry operated by 26 facilities in the western part of Japan, including university hospitals, community hospitals, and clinics. This study enrolled 1847 patients registered between September 2019 and December 2021, with 199 (10.8%) having a family history of psoriasis. Patients with a family history of psoriasis had significantly earlier onset of the disease than those without a family history. Furthermore, patients with a family history of psoriasis had significantly longer disease duration. Psoriatic arthritis (PsA) was significantly more common in patients with a family history (69/199, 34.7%) than in those without a family history (439/1648, 26.6%) (adjusted P = 0.023). A subanalysis of patients with PsA revealed a significant difference in the patient global assessment (PaGA) score in Fisher's exact test and adjusted test. The numbers of patients with PaGA 0/1 were 29 (43.3%) and 172 (39.9%) in patients with PsA with and without family history of psoriasis, respectively, whereas the numbers of patients with PaGA 3/4 were 13 (19.4%) and 145 (33.6%) in patients with PsA with and without family history of psoriasis, respectively. Other disease severity variables did not show a difference between the two groups. Our findings suggest that genetics play a larger role in the development of PsA than in the development of psoriasis vulgaris. Most cases of PsA occur in patients who already have psoriasis, therefore dermatologists should pay attention to joint symptoms, especially in patients with psoriasis who have a family history of psoriasis.

Prevalence of skin diseases and prognosis of atopic dermatitis in primary school children in populated areas of Japan from 2010 to 2019: The Asa Study in Hiroshima, Japan.

Skin diseases are common in children. However, the prevalence of childhood skin diseases in Japan has not been reported extensively. In this study, dermatologists conducted face-to-face examinations of primary school children over a 10-year period to determine the prevalence of each skin disease. Atopic dermatitis (AD, 12.3%) was the most common disease among first graders, followed by eczema other than AD (9.7%), molluscum contagiosum (1.9%), and verruca vulgaris (1.1%). Among sixth graders, acne vulgaris was most common (9.6%), followed by AD (8.9%), eczema other than AD (6.7%), and verruca vulgaris (3.1%). The prevalence of AD remained stable among first graders after 2010, at approximately 10%-15%, but it increased slightly among sixth graders. Of the 87 children who had AD in first grade, 51 (58.6%) were in remission in sixth grade. On the other hand, AD was diagnosed in 30 (4.5%) sixth graders who had been among the 665 children who did not have it in first grade. The more severe the symptoms were in first grade, the more likely a child was to still have AD in sixth grade, and the more severe the later symptoms tended to be. This study investigated recent trends in skin diseases in Japanese primary school children and found that the prevalence of some skin diseases differed between first and sixth graders. It was also found that children with moderate AD in first grade were more likely to be moderate in sixth grade than those with mild AD.

Mycobacterium tuberculosis infection in psoriatic patients treated with biologics: Real-world data from 18 Japanese facilities.

Although rare, tuberculosis has been reported with biologic treatment against psoriasis in Japan, a tuberculosis medium-burden country. Mycobacterial infection often develops after a long incubation period and might not have been adequately identified in clinical trials or post-marketing surveillance. To determine the real-world incidence of tuberculosis in psoriatic patients treated with biologics, we conducted a retrospective, multicenter, observational study in 18 facilities in Western Japan. Psoriatic patients who visited a participating facility between 2010 and March 2017 and received biologic reagents were enrolled. Information on sex, age at first biologic treatment, results of interferon-γ release assay (IGRA) for Mycobacterium tuberculosis, treatment history with isoniazid, and onset of active and/or latent tuberculosis was collected. A total of 1117 patients (830 men and 287 women) were enrolled. The mean duration of biologic treatment was 3.54 years. Sixty-five patients (5.8%) showed positive IGRA results at screening. Active tuberculosis developed in two patients after the administration of tumor necrosis factor inhibitors (both involved miliary tuberculosis). Latent tuberculosis was observed in two patients treated with anti-interleukin-12/23p40 antibody. The incidence rate of tuberculosis, including latent tuberculosis, in this survey was 0.36%. Although the incidence rate of tuberculosis was low considering the observation period of biologic treatment, active tuberculosis was found in both the screening-negative group and a screening-positive subject after isoniazid prophylaxis (both miliary tuberculosis), concluding that negative screening or isoniazid treatment does not always assure that an individual has no tuberculosis. Hence, dermatologists still need to pay careful attention to tuberculosis at every patient visit.

Cross-sectional multicenter observational study of psoriatic arthritis in Japanese patients: Relationship between skin and joint symptoms and results of treatment with tumor necrosis factor-α inhibitors.

Psoriatic arthritis (PsA) is an inflammatory arthritis with as yet unclear pathophysiology. This retrospective, multicenter, cross-sectional study was conducted in 19 facilities in western Japan and aimed to identify patients' characteristics and factors that affect the results of treatment with biologic agents. Of 2116 patients with psoriasis, 285 (13.5%) had PsA. Skin manifestations preceded joint manifestations in 69.8%, the onset was simultaneous in 17.2%, whereas PsA preceded skin manifestations in 2.5%. Peripheral arthritis was most common, occurring in 73.7%, compared with axial disease in 21.8%, enthesitis in 23.5% and dactylitis in 35.4%. Patients with severe skin manifestations were significantly younger at onset (P = 0.02) and more frequently had axial disease (P < 0.01). Biologic agents were used in 206 patients (72.3%), anti-tumor necrosis factor (TNF)-α antibodies being prescribed first to 157 of them. Anti-TNF-α antibodies were continued by 105 participants and discontinued by 47, the remaining five patients being lost to follow up. Patients who discontinued anti-TNF-α antibodies were significantly older than those who continued (55 vs 51 years, P = 0.04) and significantly older at onset of joint manifestations (50 vs 44 years, P = 0.01). Multivariate analysis revealed that patients over 50 years significantly more frequently terminated anti-TNF-α antibodies (P < 0.01). In conclusion, patients with PsA and severe skin manifestations have earlier onset and axial disease, which seriously impacts on quality of life. Anti-TNF-α antibodies were generally effective enough to continue but less so in patients aged over 50 years. Further detailed research is needed.

Aggressive treatment in paediatric or young patients with drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is associated with future development of type III polyglandular autoimmune syndrome.

We experienced a 6-year-old case of drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) with subsequent development autoimmune thyroiditis (Hashimoto's thyroiditis), type 1 diabetes with antithyroglobulin, thyroid peroxidase, insulinoma-associated antigen and anti-insulin antibodies at 4 months, alopecia at 7 months, vitiligo, uveitis due to Vogt-Koyanagi-Harada disease at 8 months after clinical resolution of the DiHS/DRESS. He was diagnosed as type III polyglandular autoimmune syndrome (PASIII) after DiHS/DRESS. Prompted by this case, we sought to determine which triggering factors were responsible for later development of PASIII in previously published cases with autoimmune sequelae. In the literature review, five patients with DIHS/DRESS were found to develop autoimmune sequelae consistent with PASIII. All cases with PASIII were much younger than those without them. Four out of the five patients were treated with intravenous immunoglobulin or pulsed prednisolone in the acute stage, although effective in short-term outcomes.

Surface plasmon resonance for cell-based clinical diagnosis.

Non-invasive real-time observations and the evaluation of living cell conditions and functions are increasingly demanded in life sciences. Surface plasmon resonance (SPR) sensors detect the refractive index (RI) changes on the surface of sensor chips in label-free and on a real-time basis. Using SPR sensors, we and other groups have developed techniques to evaluate living cells' reactions in response to stimuli without any labeling in a real-time manner. The SPR imaging (SPRI) system for living cells may visualize single cell reactions and has the potential to expand application of SPR cell sensing for clinical diagnosis, such as multi-array cell diagnostic systems and detection of malignant cells among normal cells in combination with rapid cell isolation techniques.

Application of SPR imaging sensor for detection of individual living cell reactions and clinical diagnosis of type I allergy.

A technique to visualize living cell activation in a real time manner without any labeling is required in the fields of life sciences and medicine. We have reported that surface plasmon resonance (SPR) sensors detect large changes of refractive index (RI) with living cells, such as mast cells, human basophils and lymphocytes. However conventional SPR sensors detect only an average change of RI with thousands of cells at detectable area on a sensor chip. Therefore, we developed an SPR imaging (SPRI) sensor with a CMOS camera and an objective lens in order to visualize RI of individual living cells and their changes upon stimuli. The SPRI sensor we developed could detect reactions of individual rat basophilic leukemia (RBL-2H3) cells and mouse keratinocyte cells in response to specific or nonspecific stimuli. Moreover, the sensor could detect the reactions of individual human basophils isolated from patients in response to antigens (allergens). Thus the technique can visualize the effect of various stimuli, inhibitors and/or conditions on cell reactions as change of intracellular RI distribution at single cell levels. Establishment of the technique to rapidly isolate cells from patient blood should enable us to utilize SPRI system as a high throughput screening system in clinical diagnosis, such as type I hypersensitivity and drug hypersensitivity, and as a tool to reveal novel phenomena in evanescent fields around plasma membranes.

Evaluation of peripheral blood basophil activation by means of surface plasmon resonance imaging.

Basophil activation in response to antigen may represent specificities of type I allergy of individuals and their reactions in the body. We previously demonstrated that surface plasmon resonance (SPR) sensor could detect the activation of human basophils in response to antigens. In this study, we further developed a technique based on SPR imaging (SPRI) system to detect reactions of individual basophils isolated from human blood, and investigated the potential of this sensor as a tool for diagnosis of type I allergy. To detect the change of refractive index (RI) in individual basophils, human basophils were isolated by negative selection with antibodies conjugated with magnetic beads, fixed on a gold film with anti-basophil antibody and stimulated with various antigens under the measurement of SPRI. The sensor could detect the reactions of individual basophils in response to specific antigens as well as non-specific activators. Moreover, the sensor well allocated two spots of basophils on a sensor chip and detected individual reactions to antigen. Thus, the technique developed in this study can visualize the effect of various stimuli or inhibitors on basophils as change of intracellular RI distribution at the single cell level. In combination with a device to rapidly isolate basophils from peripheral blood, this technique may be a useful tool as a high throughput screening system in clinical diagnosis for type I allergy.